PROJECT ABSTRACT Diabetic foot ulcers (DFU) are a common, disabling, and costly condition. They result from a confluence of neuropathy, immunopathy, and vasculopathy that afflict the diabetic foot. Between 15-25% of individuals with diabetes will get a DFU at some point during their lifetime, and up to 20% of these DFUs will lead to a major limb amputation. DFUs require considerable time and resources to heal, and up to 80% of those that heal may develop recurrence. As the global prevalence of diabetes continues to grow, the burden of DFU mandates more effective prevention and treatment approaches. Evolving technologies in areas such as molecular medicine, biomaterials, and biosensors offer opportunities to improve prevention and prognosis, accelerate healing, and reduce recurrence. However, the development of effective treatments for DFU has been hampered by challenges in clinical trials, including the need for better staging, validated surrogate biomarkers, and standardized endpoints. The Diabetic Foot Consortium (DFC) is being established by NIDDK to address this unmet need via a network of Clinical Research Units (CRUs), initially focused on biomarker studies. In this application, the investigators propose the UCSF Diabetic Foot Clinical Research Unit, which leverages a very diverse patient population, world-class institutions for clinical and translational science, and an experienced, multi-disciplinary team of investigators and staff. The UCSF Diabetic Foot CRU includes the University of California, San Francisco (UCSF) Medical Center and Zuckerberg San Francisco General (ZSFG) Hospital as integrated performance sites. It builds upon existing centers of clinical and research expertise, including the UCSF Center for Limb Preservation; the UCSF Diabetes Center; the UCSF Center for Vulnerable Populations; the UCSF Clinical and Translational Science Institute (CTSI); and an NIDDK-funded Center for Type 2 Diabetes Translational Research (CDTR). The investigators bring a broad range of expertise in diabetes, vascular disease, podiatric medicine/surgery, clinical trials, research measurements in ethnically/socio-economically diverse patients, and biomarker and wound healing studies of direct relevance to the goals of the DFC. They propose a Diabetic Foot CRU that will utilize coordinated management and innovative clinical research strategies to address three Specific Aims: i) recruitment of a socio-economically and ethnically diverse and representative population for biomarker studies in DFU; ii) retention of subjects for longitudinal cohort studies with repeated measures; and iii) efficient, quality-controlled, sample and data collection to enable biomarker validation studies. In addition, the investigators will contribute to the DFC by suggesting relevant biomarkers, technologies, and study protocols and trial designs to advance the clinical science of DFU care.